Molecular interactions of antibodies with PD-1/PD-L1 proteins | Immunotherapy
Aim: To compare the protein–protein interactions of antibodies targeting PD-1 and its ligand (PD-L1) with their targets in an attempt to explain the antibodies’ binding affinity. Materials & methods: The structural features of complexes between pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab and PD-1/PD-L1 are described, with the use of software and based on crystallographic data. Results: Pembrolizumab has more structural features, including the number and type of the bonds and total binding surface area, which could rationalize its different clinical behavior compared with nivolumab. Similarly, protein–protein interactions with PD-L1 differ among durvalumab, atezolizumab and avelumab. Conclusion: Differential protein–protein interactions between antibodies and PD-1/PD-L1 may indicate differential clinical activity; however, further research is needed to provide evidence.